Neurotransmitter interactions and anatomical loci of specific brain sites involved in the self-administration behavior of stimulant drugs are investigated in rats. The role of each transmitter system is studied using pharmacological manipulations and neurotoxic destruction of individual cell body and terminal regions. Neurotoxin induced lesions are used to determine the modulating influence of serotonergic neurons in the limbic and mesolimibic areas, to ascertain local norepinephrine and dopamine turnover, and to determine the influence of dopamine neurons in the nucleus accumbens on self-injection behavior. Noradrenergic and peptidergic (substance-P and opioid peptides) neurons are examined for their effects on self-injecton behavior and monoamine turnover. To substantiate the lesion studies, pemoline is compared to the test drugs, d-amphetamine and methylphenidate.